Instructions Avero tablets 24 mg No. 60
Composition
active ingredient: betahistine dihydrochloride;
1 tablet contains betahistine dihydrochloride 8 mg, 16 mg or 24 mg;
Excipients: povidone K 90, microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silicon dioxide, crospovidone, stearic acid.
Dosage form
Pills.
Main physicochemical properties:
8 mg tablets: white or almost white, round, flat, with beveled edges on both sides, embossed with "B8" on one side of the tablet and smooth on the other side;
16 mg tablets: white or almost white, round, flat, with beveled edges on both sides, with embossed marking "B16" on one side of the tablet and a dividing line on the other side;
24 mg tablets: white or almost white, round, biconvex, with a score on one side.
Pharmacotherapeutic group
Drugs for the treatment of vestibular disorders. Betahistine.
ATX code N07C A01.
Pharmacological properties
Pharmacodynamics.
The mechanism of action of betahistine is only partially understood. There are several plausible hypotheses that have been supported by animal and human studies.
The effect of betahistine on the histaminergic system
Betahistine has been shown to have partial agonist activity at H1 receptors and antagonist activity at histamine H3 receptors in nervous tissue, with little activity at histamine H2 receptors. Betahistine increases histamine metabolism and release by blocking presynaptic H3 receptors and inducing a process of downregulation of the corresponding H3 receptors.
Betahistine may increase blood flow in the cochlear area as well as throughout the brain
Pharmacological studies in animals have shown an improvement in blood flow in the striae vascularis of the inner ear, possibly by relaxing precapillary sphincters in the inner ear microcirculation system. Betahistine has also been shown to increase cerebral blood flow in humans.
Betahistine promotes vestibular compensation
Betahistine accelerates the recovery of vestibular function after unilateral neurectomy in animals by stimulating and promoting the process of central vestibular compensation. This effect is characterized by increased regulation of histamine metabolism and release and is realized as a result of H3-receptor antagonism. In humans, treatment with betahistine also reduced the time to recovery of vestibular function after neurectomy.
Betahistine alters neuronal activity in the vestibular nuclei
It was also found that betahistine has a dose-dependent inhibitory effect on the generation of spike potentials in neurons of the lateral and medial vestibular nuclei.
The pharmacodynamic properties of betahistine, as shown in animals, may provide a positive therapeutic effect of the drug in the vestibular system.
The effectiveness of betahistine has been shown in studies in patients with vestibular vertigo and Ménière's disease, as demonstrated by a reduction in the severity and frequency of vertigo attacks.
Pharmacokinetics.
Absorption
When administered orally, betahistine is rapidly and almost completely absorbed from all parts of the gastrointestinal tract. After absorption, the drug is rapidly and almost completely metabolized to form the metabolite 2-pyridylacetic acid. The concentration of betahistine in blood plasma is very low. Therefore, all pharmacokinetic analyses are carried out by measuring the concentration of the metabolite 2-pyridylacetic acid in plasma and urine.
When the drug is taken with food, the maximum concentration (Cmax) of the drug is lower than when taken on an empty stomach. At the same time, the total absorption of betahistine is identical in both cases, which indicates that food intake only slows down the absorption process of the drug.
Distribution
The percentage of betahistine bound to blood plasma proteins is less than 5%.
Biotransformation
After absorption, betahistine is rapidly and almost completely metabolized to 2-pyridylacetic acid (which has no pharmacological activity).
After oral administration of betahistine, the concentration of 2-pyridylacetic acid in blood plasma (and urine) reaches its maximum 1 hour after administration and decreases with a half-life of approximately 3.5 hours.
Breeding
2-Pyridylacetic acid is rapidly excreted in the urine. When taking the drug in a dose of 8-48 mg, approximately 85% of the initial dose is found in the urine. Excretion of betahistine by the kidneys or with feces is insignificant.
Linearity
The recovery rate remains constant over the oral dose range of 8–48 mg, indicating linear pharmacokinetics of betahistine and suggesting that the metabolic pathway involved is non-saturable.
Indication
Meniere's disease and syndrome, which are characterized by three main symptoms:
- dizziness, sometimes accompanied by nausea and vomiting;
- hearing loss (hearing loss);
- tinnitus.
Symptomatic treatment of vestibular vertigo of various origins.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the drug.
Interaction with other drugs and other types of interactions.
In vivo studies to investigate interactions with other medicinal products have not been conducted. Based on in vitro data, inhibition of cytochrome P450 enzyme activity in vivo is not expected.
In vitro data indicate inhibition of betahistine metabolism by drugs that inhibit monoamine oxidase (MAO) activity, including MAO subtype B (e.g. selegiline). Caution is recommended when betahistine is used concomitantly with MAO inhibitors (including B-selective MAO inhibitors).
Since betahistine is a histamine analogue, the interaction of betahistine with antihistamines could theoretically affect the effectiveness of one of these drugs.
Application features
During treatment with the drug, it is necessary to carefully monitor the condition of patients with bronchial asthma and/or a history of gastric and duodenal ulcers.
The drug should be prescribed with caution to patients with urticaria, rashes, or allergic rhinitis due to the risk of worsening these symptoms.
The drug should be prescribed with caution to patients with severe hypotension.
Lactose
Avero contains lactose:
The 8 mg tablet contains 70 mg of lactose.
A 16 mg tablet contains 140 mg of lactose.
A 24 mg tablet contains 210 mg of lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
Pregnancy: There are no adequate data from the use of betahistine in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at doses relevant to those used in clinical practice. Betahistine should not be used during pregnancy unless clearly necessary.
Breastfeeding. It is not known whether betahistine is excreted in human milk. Betahistine is excreted in rat milk. Effects observed after delivery in animal studies were only observed at very high doses. The benefit of the drug to the mother should be weighed against the benefits of breastfeeding and the potential risk to the child.
Fertility: Studies in rats have shown no effect on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Betahistine is indicated for the treatment of Ménière's syndrome, characterized by a triad of main symptoms: dizziness, hearing loss, tinnitus, and for the symptomatic treatment of vestibular vertigo. Both conditions may adversely affect the ability to drive and use machines. According to clinical studies investigating the effect of the drug on the ability to drive and use machines, betahistine had no or negligible influence on this ability.
Interaction with other medicinal products and other types of interactions
In vivo studies to investigate interactions with other medicinal products have not been conducted. Based on in vitro data, inhibition of cytochrome P450 enzyme activity in vivo is not expected.
In vitro data indicate inhibition of betahistine metabolism by drugs that inhibit monoamine oxidase (MAO) activity, including MAO subtype B (e.g. selegiline). Caution is recommended when betahistine is used concomitantly with MAO inhibitors (including B-selective MAO inhibitors).
Since betahistine is a histamine analogue, the interaction of betahistine with antihistamines could theoretically affect the effectiveness of one of these drugs.
Method of administration and doses
The daily dose for adults is 24–48 mg, which is evenly distributed throughout the day. The tablets should be swallowed with water.
| 8 mg tablets | 16 mg tablets | 24 mg tablets |
1–2 tablets 3 times a day | ½–1 tablet 3 times a day | 1 tablet 2 times a day |
The dose should be adjusted individually, depending on the effect. A reduction in symptoms is sometimes observed only after several weeks of treatment. The best results are sometimes achieved when the drug is taken for several months. According to some reports, prescribing treatment early in the disease prevents its progression or hearing loss in the later stages.
Averol can be taken without regard to food intake. Minor gastrointestinal disturbances may occur during treatment (listed in the "Adverse Reactions" section), which can be avoided by taking the drug with food.
Elderly patients
Although clinical trial data in this patient group are currently limited, extensive post-marketing experience suggests that dose adjustment is not necessary for elderly patients.
Kidney failure
No specific clinical trials have been conducted in this patient group, but based on post-marketing experience, no dose adjustment is required.
No specific clinical trials have been conducted in this patient group, but based on post-marketing experience, no dose adjustment is required.
Children.
Due to insufficient data on the safety and efficacy of Avero, it is not recommended for use in children (under 18 years of age).
Overdose
Several cases of overdose of the drug are known. Some patients experienced mild to moderate symptoms (nausea, drowsiness, abdominal pain) after taking the drug in doses up to 640 mg. More serious complications (convulsions, cardiopulmonary complications) were observed with intentional intake of increased doses of betahistine, especially in combination with overdose of other drugs.
Overdose treatment
Treatment of overdose should include standard supportive measures.
Adverse reactions
The following adverse reactions were observed in patients taking Avero during placebo-controlled studies with the following frequencies: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000).
Gastrointestinal tract
Common: nausea and dyspepsia.
From the nervous system
Common: headache.
In addition to cases reported during clinical trials, the following adverse reactions have been reported spontaneously during post-marketing use and from the scientific literature. The frequency cannot be estimated from the available data and is therefore classified as unknown.
On the part of the immune system
Hypersensitivity reactions, such as anaphylaxis.
Gastrointestinal tract
Complaints of minor stomach upset (vomiting, gastrointestinal pain, bloating and flatulence). These side effects usually disappear when the drug is taken with food or after reducing the dose.
Skin and subcutaneous tissue disorders
Hypersensitivity reactions of the skin and subcutaneous tissue, including angioedema, urticaria, rash and pruritus, have been observed.
Application features
During treatment with the drug, it is necessary to carefully monitor the condition of patients with bronchial asthma and/or a history of gastric and duodenal ulcers.
The drug should be prescribed with caution to patients with urticaria, rashes, or allergic rhinitis due to the risk of worsening these symptoms.
The drug should be prescribed with caution to patients with severe hypotension.
Lactose
Avero contains lactose:
The 8 mg tablet contains 70 mg of lactose.
A 16 mg tablet contains 140 mg of lactose.
A 24 mg tablet contains 210 mg of lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding.
Pregnancy: There are no adequate data from the use of betahistine in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at doses relevant to those used in clinical practice. Betahistine should not be used during pregnancy unless clearly necessary.
Breastfeeding. It is not known whether betahistine is excreted in human milk. Betahistine is excreted in rat milk. Effects observed after delivery in animal studies were only observed at very high doses. The benefit of the drug to the mother should be weighed against the benefits of breastfeeding and the potential risk to the child.
Fertility: Studies in rats have shown no effect on fertility.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
Betahistine is indicated for the treatment of Ménière's syndrome, characterized by a triad of main symptoms: dizziness, hearing loss, tinnitus, and for the symptomatic treatment of vestibular vertigo. Both conditions may adversely affect the ability to drive and use machines. According to clinical studies investigating the effect of the drug on the ability to drive and use machines, betahistine had no or negligible influence on this ability.
Expiration date
3 years.
Storage conditions
Keep out of reach of children.
Store in the original packaging in a place protected from moisture.
Store at a temperature not exceeding 25 °C.
Packaging
8 mg tablets: 10 tablets in a blister; 3 blisters in a cardboard box.
16 mg tablets: 10 tablets in a blister; 3 blisters in a cardboard box. 15 tablets in a blister; 2 blisters in a cardboard box.
24 mg tablets: 10 tablets in a blister; 3 or 6 blisters in a cardboard box. 15 tablets in a blister; 2 or 4 blisters in a cardboard box.
Side effects
The following adverse reactions were observed in patients taking Avero during placebo-controlled studies with the following frequencies: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000).
Gastrointestinal tract
Common: nausea and dyspepsia.
From the nervous system
In addition to cases reported during clinical trials, the following adverse reactions have been reported spontaneously during post-marketing use and from the scientific literature. The frequency cannot be estimated from the available data and is therefore classified as unknown.
On the part of the immune system
Hypersensitivity reactions, such as anaphylaxis.
Gastrointestinal tract
Complaints of minor stomach upset (vomiting, gastrointestinal pain, bloating and flatulence). These side effects usually disappear when the drug is taken with food or after reducing the dose.
Skin and subcutaneous tissue disorders
Hypersensitivity reactions of the skin and subcutaneous tissue, including angioedema, urticaria, rash and pruritus, have been observed.
Vacation category
According to the recipe.
Producer
Pharmaceutical Plant "POLPHARMA" S.A./
Pharmaceutical Works "POLPHARMA" SA
Location of the manufacturer and address of its place of business.
Production branch in Nowa Dębka, Metalowca Street 2, 39-460 Nowa Dębka, Poland.
Production Department in Nowa Deba, 2 Metalowca Str., 39-460 Nowa Deba, Poland.
Address
Production branch in Nowa Dębka, Metalowca Street 2, 39-460 Nowa Dębka, Poland.
Production Department in Nowa Deba, 2 Metalowca Str., 39-460 Nowa Deba, Poland.
